Introduction of diffusion tensor imaging (DTI) in 1980 and its advancement in the last three decades offered the possibility to visualize and quantify changes in white matter. DTI allows the evaluation of the structural integrity in complex neurodegenerative diseases, such as Alzheimer's disease (AD). Progressive disintegration of functional and structural neural network coordination contributes to the cognitive dysfunction in AD. Therefore, detection of loss of cortico-cortical projections may support an early diagnosis at prodromal stages of disease which may prove essential for future preventive AD treatment trials. Moreover, structural integrity measured by DTI may help to distinguish between symptomatic and disease modifying effects of pharmacological interventions. This review gives a concise account on the physical basis of DTI acquisition and processing. We summarize DTI findings in normal aging and AD and regarding the effects of cognitive intervention and antidementive treatment on structural neural connectivity. Finally, we evaluate the promising future potential of DTI to become a surrogate endpoint in clinical AD trials.